Emergence and dissemination of resistance is an inevitable consequence of the evolutionary dynamic set in motion by the introduction of antibiotics, irrespective of structural class or mode of action (Shapiro S. 2013. Speculative strategies for new antibacterials: all roads should not lead to Rome. J. Antibiot. 66: 371-386). Spread of resistance amongst clinically relevant pathogens has had an especially strong impact on the value of β-lactam antibiotics, heretofore regarded as very safe and efficacious therapies for serious bacterial infections. The appearance of new and aggressive β-lactamases, particularly extended spectrum β-lactamases (ESBLs) and other class A enzymes, has compromised the ability of β-lactams to combat infections, highlighting the need for development of new products (Fisher J F, Meroueh S O, Mobashery S. 2005. Bacterial resistance to β-lactam antibiotics: compelling opportunism, compelling opportunity. Chem. Rev. 105: 395-424). Whilst several β-lactamase inhibitors, which protect β-lactam antibiotics from hydrolysis, have been used in combination with some β-lactams, the capability of these β-lactamase inhibitors to preserve the antibacterial activity of β-lactams has eroded severely during the past decade, necessitating the search for new, more potent β-lactamase inhibitors to restore therapeutic utility of their β-lactam partners (Watkins R R, Papp-Wallace K M, Drawz S M, Bonomo R A. 2013. Novel β-lactamase inhibitors: a therapeutic hope against the scourge of multidrug resistance. Front. Microbiol. 4: 392).
WO 2008/010048 discloses β-lactamase inhibitors having the following formula:

The β-lactamase inhibitors disclosed in WO 2008/010048 includes the compound (2S,3S,5R)-3-methyl-3-((3-methyl-1H-1,2,3-triazol-3-ium-1-yl)methyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate 4,4-dioxide (formula A):

The R group is formed by a substitution reaction, for example by reaction with methyl iodide in the case of formula (A).
WO 2008/010048 discloses formation of amorphous compounds isolated by filtering and lyophilisation.
It is an object of the invention to provide an improved process for manufacture of 2-methyl penam derivatives.
It is a further object of the invention to provide a process for manufacture of 2-methyl penam derivatives that is suitable for industrial-scale manufacture.